This invention relates to noninvasive monitoring of conditions that may contribute to cardiac malfunctioning by pulsatile measurements in a limb.
Many people die suddenly of heart disease without prior symptoms. A recent consensus definition of a vulnerable patient has been evolved by medical professionals to identify people prone to sudden cardiac death [Naghavi, et al., 2003]. The definition provides a framework to combine the risks due to the formation of plaques in the blood vessels (“Vulnerable Plaque”), blood clots (“Vulnerable Blood”), and failing heart musculature (“Vulnerable Myocardium”). They define a vulnerable plaque as a future culprit plaque. It denotes the likelihood of having a cardiac event in the future. They recommend a combination of structural and functional methods for plaque characterization as this may provide higher predictive value than a single approach. However, they primarily catalogue structural methods, for use on coronary and carotid arteries. Arteries in the lower leg can be an effective substitute to evaluate the disease extent [Faxon and Creager, 2004] as atherosclerosis is a systemic disease. Available diagnostic methods characterize plaques into three categories: structural, regulatory, and functional.
Shankar [U.S. Pat. Nos. 5,343,867; 5,297,556; and 5,241,963] developed a functional measure, related to maximal compliance of the artery, a measure of relative contents of elastin and collagen in the artery. It is significantly less expensive to perform, and more sensitive, especially for pre-clinical atherosclerosis; however, it is slow, requires a separate measurement of blood pressure, and does not fully exploit the potential dynamic range. Current methods of blood pressure measurement also have observer and process errors.
Raines' Patents [U.S. Pat. Nos. 6,149,587; 5,630,424; and 5,718,232] added automated calibration to a chamber (or air or mechanical) plethysmograph (plethysmographs measure changes in volume) and measured near-maximal compliance of the artery, and combined with several other measures, such as ABI (Arm-Brachial Index) and Framingham risk profile (FRP). Raines also [U.S. Pat. No. 6,152,881] used reactive hyperemia to “activate” the endothelium and measure maximal compliance in the arm under FMD conditions.
EECP (enhanced external counterpulsation) is a last resort method that aids an ischemic heart with inflatable cuffs that are wrapped around the patient's legs at the calves and at the lower and upper thighs [Bonetti, et al., 2003]. A computer-guided device inflates and rapidly deflates them, sequentially, during diastole. That aids venous return to the heart and provides symptomatic relief. However, the method would not be useful for peripheral hemodynamic evaluation and is primarily used to substitute and enhance the effectiveness of venous pressure stockings.
This invention also uses the same apparatus to detect propensity towards inappropriate internal blood clotting in a vulnerable patient. This invention exploits pathological changes in blood viscosity to obtain pulsatile methods with large dynamic range. High blood viscosity results from increased fibrinogen and platelet counts (Blood factors involved in clot formation), higher number of white blood cells (which increase during infection and inflammation), increased number of red blood cells, and reduced deformability of red blood cells. All these changes can occur during the atherosclerotic disease progression, and can speed up prior to an acute event of injury or death of heart muscle tissue. Thus, high blood viscosity is a simple and sensitive indicator of internal blood clotting. Blood viscosity is currently measured using blood drawn from the person, by quantifying certain blood markers, such as fibrinogen and D-Dimer, at a high shear rate [DeLoughery, 1999; Turgeon, 1993]. Shear rate is a measure of the velocity gradient across the lumen of a vessel. At low shear rates red blood cell aggregation occurs and in-vitro (outside the body) techniques (unpublished) to uncover this may be under development [Hathcock, 2006]. Viscosity is asymptotically constant at high shear rates [Dormandy, 1974] and may show a dynamic range of 10 with shear rates [Hathcock, 2006]. Stagnant blood, however, is more susceptible to clotting, has higher viscosity, and has a wider separation between persons who are healthy and atherosclerotic. Plasma viscosity, as well as fibrinogen and WBC (white blood cell) counts, is positively associated with coronary heart disease (CHD) events [Koenig et al., 1998]. Furthermore, a positive relationship between plasma viscosity and the severity of CHD has been shown [Junker et al., 1998]. Venous Occlusion Plethysmography [Webster, 1998] is a noninvasive technique that can evaluate thrombosis (internal clots) in veins.